Psychological reactance theory assumes that the restriction of valued behaviors elicits anger and negative cognitions, motivating actions to regain the limited freedom. Two studies investigated the effects of two possible restrictions affecting COVID-19 vaccination: the limitation of non-vaccination by mandates and the limitation of vaccination by scarce vaccine supply. In the first study, we compared reactance about mandatory and scarce vaccination scenarios and the moderating effect of vaccination intentions, employing a German quota-representative sample (N = 973). In the preregistered second study, we replicated effects with an American sample (N = 1394) and investigated the consequences of reactance on various behavioral intentions. Results revealed that reactance was stronger when a priori vaccination intentions were low and a mandate was introduced or when vaccination intentions were high and vaccines were scarce. In both cases, reactance increased intentions to take actions against the restriction. Further, reactance due to a mandate was positively associated with intentions to avoid the COVID-19 vaccination and an unrelated chickenpox vaccination; it was negatively associated with intentions to show protective behaviors limiting the spread of the coronavirus. Opposite intentions were observed when vaccination was scarce. The findings can help policy-makers to curb the spread of infectious diseases such as COVID-19.